Several lines of evidence point to the involvement of somatic mutations in the mechanism of action of carcinogens. There is also reason to think that DNA repair plays a role in carcinogenesis. For example, we have recently demonstrated that kin fibroblasts from non-malignant tissue of xeroderma pigmentosum (XP) patients (abnormally high incidence of sunlight-induced skin cancer) exhibit higher than normal frequencies of mutations induced by UV; this, not only in classical XP (defective excision repair) but also in XP variants (defective post replication repair). These findings link higher incidence of skin cancer, increased susceptibility to UV-induced mutations, and defective DNA repair. We also find that such XP cells are abnormally senstitive to the cytotoxic action of active forms of aromatic amides and to MNNG. (It appears that hydrocarbon-induced mutations are also higher in XP cells than in normal human cells from our preliminary results.) Since this points to the involvement of different kinds of DNA repair defects in enhancing the cytotoxic and mutagenic action of carcinogens, we will investigate the question using, in addition to our XP cells, cells derived from persons with two other forms of genetic pre-disposition to cancer., viz., ataxia telangiectasia (AT) (sensitive to X-rays) and Fanconi's anemia (FA) (sensitive to mitomycin C). With such cells we will: A. investigate the effect of DNA EXCISION REPAIR on the mutagenicity of carcinogens; B. investigate the effect of POST-REPLICATION REPAIR on such action. For these studies we will utilize, where applicable, radioactively-labeled carcinogens to determine the number and kinds of DNA-carcinogen adducts which corollate with the induction of mutations in these human cells.